Histamine (HA) neurons have been implicated in several central nervous systems (CNS) functions, e.g., control of water homeostasis, body temperature, blood pressure and in psychiatric disorders, namely depression. HA neurons have been described in the CNS based upon biochemical and pharmacological experiments but have not heretofore been characterized anatomically because no histologic method is as yet available for their selective visualization. The purpose of this project is to prepare a specific antiserum against rat histidine decarboxylase (HDC) which will be used to analyze by immunocytochemistry the anatomic organization of HA neurons in the rat brain. An antiserum against HDC will be used in combination with the immunofluorescence and peroxidase antiperoxidase (PAP) technique to identify and localize cell bodies of HA neurons. The PAP technique applied to 100 micron thick sections will be employed to analyze the dendritic configuration of HA neurons; these data will serve as a basis for identifying afferents to these neurons. The distribution of HA axons and terminals in the rat CNS will be described at the light microscopic level and it will be examined whether there exist differential projections from different HA cell groups. In cerebral cortex the regional and laminar distribution of HA axons will be analyzed. The PAP technique will be employed with modifications to visualize HDC at the ultrastructural level for identification of the types and distribution of contacts made by HA axons on target cells. Based on the immunocytochemical data lesions will be performed to correlate changes in biochemical parameters of HA neurons with histochemical data to obtain information about a possible localization of histamine and histidine decarboxylase in non-neuronal compartments such as mast cells.